Analysis of tissue remodeling mechanisms by circulating blood cells during human reproduction

尽管卵巢性类固醇激素诱导子宫内膜分化以利于胚胎着床已被广泛接受，但关于人胚胎附着于子宫内膜上皮的确切分子机制仍不清楚。因此，在辅助生殖技术领域，接受体外受精和胚胎移植治疗的患者的植入失败越来越受到关注。另一方面，在过去的几十年中，建立母体对胚胎的免疫耐受的机制已在生殖免疫学中进行了研究。最近，越来越多的证据表明，激活的免疫细胞积极促进怀孕的建立。与此相一致，我们发现外周血免疫细胞积极影响母体子宫内膜和妊娠黄体的功能和分化，以促进早期妊娠的胚胎着床。此外，血小板被证明可以调节黄体和胎盘形成中的血管重塑过程。基于这些发现，我们已经成功地开发了一种新的治疗植入失败的患者使用自体外周血免疫细胞。

Although it has been widely accepted that adequate endometrial differentiation for embryo implantation is induced by ovarian sex steroid hormones, the precise molecular mechanism(s) concerning human embryo attachment to endometrial epithelium remains unclear. Accordingly, implantation failure in patients treated with in vitro fertilization and embryo transfer has been increasingly focused on in the field of assisted reproductive technology. On the other hand, during the past several decades the mechanisms for establishing maternal immune tolerance against embryo have been investigated in reproductive immunology. Recently, accumulating evidence suggests that activated immune cells actively contribute to establishment of pregnancy. In accordance with it, we found that peripheral blood immune cells positively affect function and differentiation of maternal endometrium and corpus luteum of pregnancy to facilitate embryo implantation during early pregnancy. In addition, platelets were shown to regulate vascular remodeling process in corpus luteum and placental formation. Based on these findings, we have successfully developed a new therapy for patients with implantation failure using autologous peripheral blood immune cells.